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抗体噬菌体展示技术及其应用。

Antibody phage display technology and its applications.

作者信息

Hoogenboom H R, de Bruïne A P, Hufton S E, Hoet R M, Arends J W, Roovers R C

机构信息

CESAME, Department of Pathology, University Hospital Maastricht, The Netherlands.

出版信息

Immunotechnology. 1998 Jun;4(1):1-20. doi: 10.1016/s1380-2933(98)00007-4.

Abstract

In recent years, the use of display vectors and in vitro selection technologies has transformed the way in which we generate ligands, such as antibodies and peptides, for a given target. Using this technology, we are now able to design repertoires of ligands from scratch and use the power of phage selection to select those ligands having the desired (biological) properties. With phage display, tailor-made antibodies may be synthesized and selected to acquire the desired affinity of binding and specificity for in vitro and in vivo diagnosis, or for immunotherapy of human disease. This review addresses recent progress in the construction of, and selection from phage antibody libraries, together with novel approaches for screening phage antibodies. As the quality of large naïve and synthetic antibody repertoires improves and libraries becomes more generally available, new and exciting applications are pioneered such as the identification of novel antigens using differential selection and the generation of receptor a(nta)gonists. A combination of the design and generation of millions to billions of different ligands, together with phage display for the isolation of binding ligands and with functional assays for identifying (and possibly selecting) bio-active ligands, will open even more challenging applications of this inspiring technology, and provide a powerful tool for drug and target discovery well into the next decade.

摘要

近年来,展示载体和体外筛选技术的应用改变了我们为特定靶点生成配体(如抗体和肽)的方式。利用这项技术,我们现在能够从头设计配体文库,并借助噬菌体筛选的力量来选择具有所需(生物学)特性的配体。通过噬菌体展示,可以合成并筛选定制抗体,以获得用于体外和体内诊断或人类疾病免疫治疗所需的结合亲和力和特异性。本文综述了噬菌体抗体文库构建和筛选方面的最新进展,以及筛选噬菌体抗体的新方法。随着大型天然和合成抗体文库质量的提高以及文库的更广泛可得,诸如使用差异筛选鉴定新型抗原和生成受体拮抗剂等新的激动人心的应用不断涌现。将设计和生成数百万至数十亿种不同配体、利用噬菌体展示分离结合配体以及通过功能测定鉴定(并可能选择)生物活性配体相结合,将开启这项鼓舞人心的技术更具挑战性的应用,并为未来十年的药物和靶点发现提供强大工具。

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